In this project, we aimed to identify genes mutated in human brain tumors, by establishing yeast-based assays for chain-terminating mutations, as a new molecular diagnostic tool. We have successfully obtained the following results.1) We have demonstrated combined mutation or deletion of p53, PTEN, p16, p14ARF genes in human glioblastoma cells (Brain Pathol, 1999).2) We have demonstrated the role of p53 mutation in malignant progression from low grade astrocytoma to glioblastoma (Oncogene, 1999, Cancer Res, 1999)3) We have established a yeast assay for p73, and applied it to human brain tumors, together with analyzing the function of the p73 C-terminal part (Cancer Res, 1999 ; Brain Pathol, 2001).4) We established a PTEN stop codon assay, and demonstrated mutation of PTEN and expression of ψPTEN in glioblastomas (Oncogene, 2000).5) We established an APC stop codon assay, and applied it to brain tumors, colon cancers, and breast cancers (Am J Pathol, 2000)6) We have established an NF2 stop codon assay and a "Universal stop codon assay", and applied them to various human tumors (manuscripts in preparation).7)さらに特定遺伝子だけではなくいかなる遺伝子にも即座に応用できるUniversal stop codon assayを開発し,APC,MLH1,MLH6,E-cadherin,BRCA1などの遺伝子に応用し,その成果を現在投稿中である.